title: Refining the assessment of contrast-induced acute kidney injury: the load-to-damage relationship.
abstract: OBJECTIVE
  Comparing the nephrotoxicity of individual contrast agents is challenging, as contrast-induced acute kidney injury (CI-AKI), a widely used trial endpoint, is unable to discriminate between contrast-related and contrast-unrelated causes of renal damage. We established a quantitative method to selectively evaluate the dose-dependent nephrotoxic effect of different contrast agents.
  
  
  METHODS
  We randomized 113 patients undergoing coronary procedures to either iodixanol 320 mg/ml or iobitridol 350 mg/ml. We calculated baseline creatinine clearance (CrCl) and postprocedural change in serum creatinine. We then calculated the regression of the individual iodine load against the creatinine maximum change [load-to-damage relationship (LDR)]. We assumed that its R estimates the predictive accuracy of contrast dose-dependent effects on renal function changes, and that the slope of the LDR characterizes the intrinsic nephrotoxicity of the contrast. We also performed a semi-quantitative evaluation of procedural complexity to assess its complementary role in postprocedural AKI.
  
  
  RESULTS
  We found significant correlations between contrast load and creatinine changes for both iobitridol (R: 0.29; P <0.0001) and iodixanol (R: 0.15; P = 0.00028). The LDR slope was, however, significantly steeper for iobitridol compared with iodixanol (19.03 ± 4.02 vs. 14.50 ± 4.63 Cr*CrCl/I; P <0.001) and in diabetic compared with nondiabetic patients (24.35 ± 4.96 vs. 4.59 ± 3.25 Cr*CrCl/I; P <0.001). Adding the procedural complexity score to the contrast load significantly increased the predictive ability of the regression model for postprocedural renal function changes (P < 0.02 for the R increase in overall population), suggesting a role for procedural complexity in postprocedural renal function damage.
  
  
  CONCLUSIONS
  The LDR slope is a promising method to evaluate the specific contrast-related fraction of postprocedural AKI.
authors.affiliation: aCardiology Unit, Misericordia Hospital, Grosseto bInterventional Cardiology, A.O. Fatebenefratelli, Milan cInstitute of Cardiology and Center of Excellence on Aging, 'G. d'Annunzio' University, Chieti, Italy.
authors.forename: Ugo
authors.initials: U
authors.lastname: Limbruno
authors.forename: Andrea
authors.initials: A
authors.lastname: Picchi
authors.forename: Andrea
authors.initials: A
authors.lastname: Micheli
authors.forename: Paolo
authors.initials: P
authors.lastname: Calabria
authors.forename: Bernardo
authors.initials: B
authors.lastname: Cortese
authors.forename: Gina
authors.initials: G
authors.lastname: Brizi
authors.forename: Silva
authors.initials: S
authors.lastname: Severi
authors.forename: Raffaele
authors.initials: R
authors.lastname: De Caterina
mesh_terms: D000368:Aged; D005260:Female; D006801:Humans; D008297:Male; D058186:Acute Kidney Injury / Q000097:blood / Q000139:chemically induced / Q000175:diagnosis; D003287:Contrast Media / Q000009:adverse effects; D017023:Coronary Angiography / Q000009:adverse effects / Q000379:methods; D003404:Creatinine / Q000097:blood; D004305:Dose-Response Relationship, Drug; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate / Q000187:drug effects; D007275:Injections, Intravenous; D007472:Iohexol / Q000009:adverse effects / Q000031:analogs & derivatives; D009203:Myocardial Infarction / Q000000981:diagnostic imaging; D011446:Prospective Studies; D014283:Triiodobenzoic Acids / Q000009:adverse effects
chemical_list: D003287:Contrast Media; D003404:Creatinine; C093233:iobitridol; C044834:iodixanol; D007472:Iohexol; D014283:Triiodobenzoic Acids